Bordetella bronchiseptica is capable of infecting the nasal passages and respiratory tracts of many animals, particularly mammals. B. bronchispectica is the cause of atrophic rhinitis and pneumonia in swine. Harris and Switzer, Am. J. Vet. Res., 30, 1161-1166 (1969). A major lesion of the disease in swine is commonly referred to as "turbinate atrophy" because following the primary B. bronchiseptica infection, the nasal turbinate bones frequently undergo serious deterioration. See Switzer and Farrington U.S. Pat. No. 4,016,253 (1977).
In dogs, B. bronchiseptica has been characterized as the primary etiological agent in infectious canine tracheobronchitis more commonly known as kennel cough. Wright et al, Vet. Rec., Nov. 3, 1973, 486-487; Appel et al, Cornell Research Laboratory for Disease of Dogs, Laboratory Report, Series 2, No. 6 (May, 1976). The latter publication states that kennel cough is a highly contagious respiratory disease of dogs which, although not life-threatening, should be prevented. The disease causes suffering to the dogs and is unpleasant for dog owners. It is commonly transmitted when dogs are placed in kennels for boarding.
Other mammalian species are also afflicted with B. bronchiseptica infections of the respiratory tract. These include laboratory animals such as guinea pigs, rabbits, and rats, as well as animals raised for meat or fur, such as rabbits and chinchilla. See Nakagawa et al, Jap. J. Vet. Sci., 33(2), 53-60 (1971); Oldenburg et al, Monatshefte fur Veterinarmedizin, 27(19), 738-743 (1972); Burek et al, Lab. An. Sci., 22(66), 844-849 (1972); Ioakimidis et al, Kteniatrika Nea Thessaloniki, 2, 31-33 (1970). As with swine and dogs, the virulent B. bronchiseptica colonize the respiratory mucosa and thereby produce the clinical symptoms of the infection. B. bronchiseptica may also cause pneumonia in monkeys and other zoo animals. Graves, Lab. An. Car., 20(2), 246-250 (1970). Cats are carries of B. bronchiseptica and may spread the disease to other animals. Fisk et al, Lab. An. Sci., 23(1), 33-35 (1973).
Because of the economic loss to swine raisers due to turbinate atrophy, which is very prevalent in the United States and other countries, there has been a major research effort to develop an effective vaccine to protect swine against B. bronchiseptica.
Switzer and Harris found that the introduction of live cells of a low-virulence strain of B. bronchiseptica into the nasal cavities of non-immune swine would cause a relatively mild infection, and that thereafter the swine would be immune to further infection, and would thereby be protected against turbinate atrophy. See J. Vet. Res., 30, 1161-1166 (July, 1969). The attenuated strain of B. bronchiseptica tested by Switzer and Harris was designated strain D-1. Although introduction of strain D-1 into the nasal passages of swine protected the swine against turbinate atrophy, it was found that strain D-1 persisted in the nasal passages and produced a mild damage to the nasal epithelium. There was no evidence of reversion to a swine virulent form of B. bronchiseptica, but is was feared that strain D-1 could infect other animals such as dogs. The need for an effective live intranasal vaccine which has no adverse effect and which does not persist on the nasal mucosa has not been met until the present invention.
Parenteral vaccines for intramuscular injection were also the subject of extensive research. One of the first such experimental vaccines was prepared from a virulent strain of B. bronchiseptica (identified as strain B), but this whole-cell vaccine failed to induce adequate resistance to nasal infection as reported by Harris and Switzer, Am. J. Vet. Res., 30, 1161-1166 (July, 1969). The cells were killed to form the bacterin.
Kasuga et al U.S. Pat. No. 3,873,691 describes a parenteral vaccine which is prepared from virulent strains of B. bronchiseptica. In order to maintain the baceteria in virulent form (referred to as Phase I form in the patent), the patent teaches that the cultures should be grown in a medium containing blood, or in a special medium containing activated carbon or an ion exchange resin. It is believed that a parenteral vaccine prepared by the method of the Kasuga et al patent has been marketed for commercial use in Japan.
In the United States, the first successful swine vaccine for preventing turbinate atrophy is manufactured and sold by the Burns-Biotec Laboratories Division of Chrommalloy Pharmaceutical, Inc. in accordance with Switzer and Farrington U.S. Pat. No. 4,016,253. This patent describes a parenteral vaccine for intramuscular injection prepared from killed whole-cells of strain D-1 (ATCC No. 31124).
The resistance to B. bronchiseptica infection induced by parenteral vaccines such as the strain D-1 vaccine is different than the immunity produced by intranasal infection of swine with live B. bronchiseptica. Parenteral vaccination does not prevent nasal infection by virulent B. bronchiseptica, although it does accelerate nasal clearance of the infection, and effectively protects against the development of the gross lesions associated with atrophtic rhinitis, and the second destruction of the turbinate bones referred to as turbinate atrophy. Further, even a mild infection of the nasal passages of parenterally vaccinated swine may make the swine more susceptible to secondary infections of the respiratory tract.
The strain D-1 parenteral vaccine used commercially for swine has not been found to be effective for immunizing dogs against B. bronchiseptica. There is an increase in the circulating antibody titer, but the dogs still contract the infection and manifest symptons of kennel cough. Further, the parenteral injection of strain D-1 vaccines may have undesirable side effects, including swelling at the site of the injection, anophylactic shock, and other toxic effects on the dogs. Some investigators (McCanldish-1976 and Shelton-1977) have reported experimental immunization of dogs against B. bronchiseptica infection with a parenteral vaccine. McCanldish et al., Vet. Rec., 98, 156-157 (1976); Shelton et al, Vet. Med./Small Animal Clinician, February, 1977, 189-193. However, another investigator (Appel-1977) has been unsuccessful in repeating the McCanldish or Shelton work. See Bemis, Greisen, and Appel, J. Infec. Disease, 135, 753-758 (May, 1977).